Therapist-led pathways have been proposed as waitlist management strategies prior to surgery for conditions such as carpal tunnel syndrome (CTS) in public hospitals. These models of care typically ...shift the initial care of patients and decision-making from surgeons to therapists and, have been shown to reduce the number of patients requiring surgery and improve wait-times. This occurs despite limited evidence of surgeon-therapist agreement on key decisions, such as the need for surgery. The purpose of this was study was to assess the agreement between therapists and orthopaedic surgeons regarding the need for surgery for patients who have CTS.
This blinded inter-rated agreement study was embedded in a multicentre randomised parallel groups trial of 105 patients with CTS referred to four orthopaedic departments and waitlisted for an appointment. The trial evaluated the effect of a therapist-led care pathway on the need for surgery and outcomes related to symptoms and function. Patients were randomised to either remain on the orthopaedic waitlist or receive group education, a splint and home exercises. The decision on the need for surgery at 6 months was made by a member of the orthopaedic consultant team or by one of the 14 participating therapists. The therapists and surgeons were blinded to each other's decision. Agreement was determined using percentage agreement, kappa coefficients (k), prevalence-adjusted and bias-adjusted kappa (PABAK), and Gwet's first-order agreement coefficient (AC1).
Substantial agreement was seen between therapists and surgeons regarding the need for surgery (PABAK=0.74 (0.60-0.88)). Agreement was significantly associated with experience (
=.02). Therapists with advanced experience and scope of practice demonstrated perfect agreement with surgeons (PABAK=1.00 (95% CI: 1.00-1.00)). Mid-career therapists demonstrated substantial agreement (PABAK=0.67 (95% CI: 0.42-0.91)) and early-career therapists demonstrated fair agreement (PABAK=0.43 (95% CI: -0.04-0.90)).
Therapists with advanced scope of practice make decisions that are consistent with orthopaedic surgeons.
Peripheral neuropathies are common conditions and can result in numbness, paresthesia, motor deficits, and pain. There is increasing evidence for the use of biomarkers as clinical indicators of the ...presence, severity, and prognosis of nerve lesions; however, biomarker identification has largely been focused on disorders of the central nervous system, and less is known about their role in the peripheral nervous system.
To assess blood-based biomarker concentrations associated with nerve involvement in patients with peripheral neuropathy compared with control participants.
Ovid, MEDLINE, Embase, and CINAHL were searched from inception to September 23, 2021.
Observational studies reporting on blood biomarkers in patients diagnosed with peripheral neuropathy were included. This review was preregistered on PROSPERO and followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Data were abstracted by 1 investigator and independently reviewed by a second.
Data were meta-analyzed when at least 2 studies reported the same biomarker with comparable methodology. Fixed-effects models were used when only 2 studies were included; random-effects models were used when more than 2 studies were included.
The outcome of interest was concentration of biomarkers.
This review included 36 studies reporting on 4414 participants, including 2113 control participants and 2301 patients with peripheral neuropathy with 13 distinct peripheral neuropathy diagnoses. Diabetic neuropathy was the most common neuropathy diagnosis (13 studies), followed by Charcot-Marie-Tooth disease (6 studies) and Guillain-Barre syndrome (6 studies). Overall, 16 different blood-based biomarkers associated with nerve involvement were evaluated. The most used were neurofilament light chain, S100B, brain-derived neurotrophic factor, and neuron-specific enolase. Patients with peripheral neuropathy demonstrated significantly higher levels of neurofilament light chain compared with controls (standardized mean difference SMD, 0.93 95% CI, 0.82 to 1.05; P < .001). There were no significant differences in levels of S100B (SMD, 1.10 95% CI, -3.08 to 5.28; P = .38), brain-derived neurotrophic factor (SMD, -0.52 95% CI, -2.23 to 1.19; P = .40), or neuron-specific enolase (SMD, -0.00 95% CI, -1.99 to 1.98; P = .10) in patients with peripheral neuropathy compared with control participants.
The findings of this systematic review and meta-analysis support the use of neurofilament light chain as a blood-based measure associated with the presence of neuronal injury in patients with peripheral neuropathy.
Longitudinal case-control animal model.
To investigate effects of mesenchymal stem cell (MSC) treatment on multifidus muscle remodeling after intervertebral disc (IVD) lesion.
Lesion and degeneration ...of IVDs cause structural remodeling of the multifidus muscle. Proinflammatory cytokines are thought to contribute. MSC treatment restores IVD health after lesion but its effects on surrounding tissues remains unknown. Using an animal model of IVD degeneration, we assessed the effects of MSC treatment of IVDs on the structural remodeling and cytokine expression within the multifidus muscle.
An anterolateral lesion was performed on the L1-2, L3-4, and L5-6 IVDs in sheep. At either 4 (early treatment) or 12 (late treatment) weeks after IVD lesion, MSCs were injected into the lesioned IVD. Multifidus muscle was harvested from L2 (gene expression analysis) and L4 (histological analysis) at 3 or 6 months after IVD lesion and naïve controls for histological analysis of muscle, adipose, and connective tissue cross-sectional areas, and immunohistochemistry to study muscle fiber types. Real-time polymerase chain reactions quantified expression of tumor necrosis factor, interleukin-1β, and transforming growth factor-β1.
MSC treatment of IVD lesion prevented the increased adipose and connective tissue cross-sectional area expected after IVD lesion. MSC treatment did not prevent slow-to-fast muscle fiber type transformation. Gene expression of proinflammatory cytokines within the muscle was altered by the MSC treatment of IVD. Increased interleukin-1β expression was prevented in the early treatment group and tumor necrosis factor and transforming growth factor-β1 expression was upregulated at 6 months.
Results show that although MSC treatment prevents fatty infiltration and fibrosis of the multifidus muscle after IVD lesion, it cannot prevent a muscle inflammatory response and muscle fiber transformation. These findings highlight the potential role of MSC therapy after IVD injury, but reveals that other interventions may also be necessary to optimize recovery of muscle.
4.
Neuropathic pain following peripheral nerve injury is associated with hyperexcitability in damaged myelinated sensory axons, which begins to normalise over time. We investigated the composition and ...distribution of shaker-type-potassium channels (Kv1 channels) within the nodal complex of myelinated axons following injury. At the neuroma that forms after damage, expression of Kv1.1 and 1.2 (normally localised to the juxtaparanode) was markedly decreased. In contrast Kv1.4 and 1.6, which were hardly detectable in the naïve state, showed increased expression within juxtaparanodes and paranodes following injury, both in rats and humans. Within the dorsal root (a site remote from injury) we noted a redistribution of Kv1-channels towards the paranode. Blockade of Kv1 channels with α-DTX after injury reinstated hyperexcitability of A-fibre axons and enhanced mechanosensitivity. Changes in the molecular composition and distribution of axonal Kv1 channels, therefore represents a protective mechanism to suppress the hyperexcitability of myelinated sensory axons that follows nerve injury.
Carpal tunnel syndrome (CTS) is the most common focal nerve injury. People with CTS may show alterations in central processing of nociceptive information. It remains unclear whether the central ...sensitization inventory (CSI) is capable of detecting such altered central pain processing.
Thirty healthy volunteers were matched with 30 people with unilateral CTS from the orthopaedic waitlist. Changes to central pain processing were established through psychophysical sensory testing (bilateral pressure pain thresholds (PPT), conditioned pain modulation, temporal summation) and pain distribution on body charts. Patients also completed pain severity and function questionnaires, psychological questionnaires and the CSI.
Compared to healthy volunteers, patients with CTS have lower PPTs over the carpal tunnel bilaterally (t = -4.06,
< 0.0001 ipsilateral and t = -4.58,
< 0.0001 contralateral) and reduced conditioned pain modulation efficacy (t = -7.31,
<0.0001) but no differences in temporal summation (t = 0.52,
= 0.60). The CSI was not associated with psychophysical measures or pain distributions indicative of altered central pain processing. However, there was a correlation of the CSI with the Beck Depression Inventory (r = 0.426;
= 0.019).
Patients with CTS show signs of altered central pain mechanisms. The CSI seems unsuitable to detect changes in central pain processing but is rather associated with psychological factors in people with focal nerve injuries.
Non-neutral wrist positions and external pressure leading to increased carpal tunnel pressure during computer use have been associated with a heightened risk of carpal tunnel syndrome (CTS). This ...study investigated whether commonly used ergonomic devices reduce carpal tunnel pressure in patients with CTS. Carpal tunnel pressure was measured in twenty-one patients with CTS before, during and after a computer mouse task using a standard mouse, a vertical mouse, a gel mouse pad and a gliding palm support. Carpal tunnel pressure increased while operating a computer mouse. Although the vertical mouse significantly reduced ulnar deviation and the gel mouse pad and gliding palm support decreased wrist extension, none of the ergonomic devices reduced carpal tunnel pressure. The findings of this study do therefore not endorse a strong recommendation for or against any of the ergonomic devices commonly recommended for patients with CTS. Selection of ergonomic devices remains dependent on personal preference.
•Computer use increases carpal tunnel pressure in patients with carpal tunnel syndrome.•Ergonomic devices alter wrist and forearm positions during computer use.•None of the tested ergonomic devices reduced carpal tunnel pressure.•A strong recommendation for or against ergonomic devices cannot be endorsed.•Selection will depend on the patient's preference until further evidence is available.
IntroductionPain constitutes a major component of the global burden of diseases. Recent studies suggest a strong genetic contribution to pain susceptibility and severity. Whereas most of the ...available evidence relies on candidate gene association or linkage studies, research on the genetic basis of pain sensitivity using genome-wide association studies (GWAS) is still in its infancy. This protocol describes a proposed GWAS on genetic contributions to baseline pain sensitivity and nociceptive sensitisation in a sample of unrelated healthy individuals of mixed Latin American ancestry.Methods and analysisA GWAS on genetic contributions to pain sensitivity in the naïve state and following nociceptive sensitisation will be conducted in unrelated healthy individuals of mixed ancestry. Mechanical and thermal pain sensitivity will be evaluated with a battery of quantitative sensory tests evaluating pain thresholds. In addition, variation in mechanical and thermal sensitisation following topical application of mustard oil to the skin will be evaluated.Ethics and disseminationThis study received ethical approval from the University College London research ethics committee (3352/001) and from the bioethics committee of the Odontology Faculty at the University of Antioquia (CONCEPTO 01–2013). Findings will be disseminated to commissioners, clinicians and service users via papers and presentations at international conferences.
Background It remains unclear whether definite neural mechanosensitivity (NM) is required for neural mobilisations to be beneficial in people with spinally referred leg pain.Objective To determine ...whether the efficacy of neural mobilisations in patients with spinally referred leg pain depends on the presence and type of criteria used to define NM.Method PubMed, CINAHL, Cochrane Central Register of Controlled Trials, PEDro and Science Direct were searched from 1980 to March 2020. Randomised controlled trials evaluating the efficacy of neural mobilisations on pain and disability in spinally referred leg pain were included. Studies were grouped according to the certainty of NM into NMdefinite, NMunclear, NMuntested and NMabsent. Effects on pain and disability and subgroup differences were examined.Results We identified 21 studies in 914 patients (3 NMdefinite, 16 NMunclear, 2 NMuntested, 0 NMabsent). Meta-analysis revealed medium to large effect sizes on pain for neurodynamic compared to control interventions in NMdefinite and NMunclear groups. For disability, neurodynamic interventions had medium to large effects in NMunclear but not NMdefinite groups. NMuntested studies could not be pooled.Conclusion The nonexistence of studies in patients with negative neurodynamic tests prevents inferences whether neural mobilisations are effective in the absence of NM. The criteria used to define NM may not impact substantially on the efficacy of neural mobilisations. The mostly high risk of bias and heterogeneity prevents firm conclusions.Clinical implications Neural mobilisations seem beneficial to reduce pain and disability in spinally referred leg pain independent of the criteria used to interpret neurodynamic tests.
IntroductionSciatica is a common condition and is associated with higher levels of pain, disability, poorer quality of life, and increased use of health resources compared with low back pain alone. ...Although many patients recover, a third develop persistent sciatica symptoms. It remains unclear, why some patients develop persistent sciatica as none of the traditionally considered clinical parameters (eg, symptom severity, routine MRI) are consistent prognostic factors.The FORECAST study (factors predicting the transition from acute to persistent pain in people with ‘sciatica’) will take a different approach by exploring mechanism-based subgroups in patients with sciatica and investigate whether a mechanism-based approach can identify factors that predict pain persistence in patients with sciatica.Methods and analysisWe will perform a prospective longitudinal cohort study including 180 people with acute/subacute sciatica. N=168 healthy participants will provide normative data. A detailed set of variables will be assessed within 3 months after sciatica onset. This will include self-reported sensory and psychosocial profiles, quantitative sensory testing, blood inflammatory markers and advanced neuroimaging. We will determine outcome with the Sciatica Bothersomeness Index and a Numerical Pain Rating Scale for leg pain severity at 3 and 12 months.We will use principal component analysis followed by clustering methods to identify subgroups. Univariate associations and machine learning methods optimised for high dimensional small data sets will be used to identify the most powerful predictors and model selection/accuracy.The results will provide crucial information about the pathophysiological drivers of sciatica symptoms and may identify prognostic factors of pain persistence.Ethics and disseminationThe FORECAST study has received ethical approval (South Central Oxford C, 18/SC/0263). The dissemination strategy will be guided by our patient and public engagement activities and will include peer-reviewed publications, conference presentations, social media and podcasts.Trial registration numberISRCTN18170726; Pre-results.
The aim of this study was to describe the development of morphologic and diffusion tensor imaging sequences of peripheral nerves at 7 T, using carpal tunnel syndrome (CTS) as a model system of focal ...nerve injury.
Morphologic images were acquired at 7 T using a balanced steady-state free precession sequence. Diffusion tensor imaging was performed using single-shot echo-planar imaging and readout-segmented echo-planar imaging sequences. Different acquisition and postprocessing methods were compared to describe the optimal analysis pipeline. Magnetic resonance imaging parameters including cross-sectional areas, signal intensity, fractional anisotropy (FA), as well as mean, axial, and radial diffusivity were compared between patients with CTS (n = 8) and healthy controls (n = 6) using analyses of covariance corrected for age (significance set at P < 0.05). Pearson correlations with Bonferroni correction were used to determine association of magnetic resonance imaging parameters with clinical measures (significance set at P < 0.01).
The 7 T acquisitions with high in-plane resolution (0.2 × 0.2mm) afforded detailed morphologic resolution of peripheral nerve fascicles. For diffusion tensor imaging, single-shot echo-planar imaging was more efficient than readout-segmented echo-planar imaging in terms of signal-to-noise ratio per unit scan time. Distortion artifacts were pronounced, but could be corrected during postprocessing. Registration of FA maps to the morphologic images was successful. The developed imaging and analysis pipeline identified lower median nerve FA (pisiform bone, 0.37 SD 0.10) and higher radial diffusivity (1.08 0.20) in patients with CTS compared with healthy controls (0.53 0.06 and 0.78 0.11, respectively, P < 0.047). Fractional anisotropy and radial diffusivity strongly correlated with patients' symptoms (r = -0.866 and 0.866, respectively, P = 0.005).
Our data demonstrate the feasibility of morphologic and diffusion peripheral nerve imaging at 7 T. Fractional anisotropy and radial diffusivity were found to be correlates of symptom severity.
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